ADGRV1 p.Cys6071Ser

Variant names:

• chr5-91072506-G-C
• NM_032119.4:c.18212G>C
• ADGRV1 p.Cys6071Ser

Your query was ambiguous. Multiple possible variants found:

• chr5-91072506-G-C
• chr5-91072505-T-A
• chr5-91072506-GC-CT
• chr5-91072506-GC-CA
• chr5-91072506-GC-CG
• chr5-91072505-TGC-AGT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032119.4(ADGRV1):​c.18212G>C​(p.Cys6071Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.46
• Publications: 0 publications found

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.18212G>C	p.Cys6071Ser	missense	Exon 86 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.18228G>C		non_coding_transcript_exon	Exon 86 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.18212G>C	p.Cys6071Ser	missense	Exon 86 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000638510.1	TSL:1	n.5479G>C		non_coding_transcript_exon	Exon 22 of 26
	ADGRV1	ENST00000425867.3	TSL:5	c.7166G>C	p.Cys2389Ser	missense	Exon 34 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.73	T
PhyloP100		9.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Varity_R		0.79
gMVP		0.76
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-90368323;